Patients with well-documented chronic non-A, non-B (non-lupoid) hepatitis are being evaluated to determine the natural history of this disease and to obtain tissues and reagents to search for non-A, non-B agents. Twenty-one patients have been admitted to this study. These patients have undergone thorough evaluation including a liver biopsy in twenty. They have had the disease for periods ranging from 1 to 8 years. Four patients have a mild degree of malaise, the remaining patients are asymptomatic. Liver biopsies have revealed chronic persistent hepatitis in five, chronic active hepatitis in eleven and cirrhosis in four. Examination of liver biopsies by electron and immunofluorescence microscopy has failed to show definitive evidence of viral antigens or viral particles. However, electron microscopy of 50% of biopsies has revealed intranuclear virus-particle-like structures which are similar to those observed in chimpanzees with non-A, non-B hepatitis. The significance and specificity of these structures is under investigation.